Anti-TB therapy following drug-induced liver injury (TB-DILI)
Research type
Research Study
Full title
Reintroduction of anti-tuberculosis therapy following drug-induced liver injury: a randomised controlled trial (TB-DILI)
IRAS ID
1005097
Contact name
Wei Shen Lim
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Eudract number
2020-004193-21
ISRCTN Number
ISRCTN92067975
Research summary
The standard 4 drug treatment for active TB is very effective if the full 6 month course is completed. However, there can be side effects. An important side effect is drug-induced liver injury (DILI). Around 1 in 14 patients may be affected. For patients experiencing these complications, treatment is usually stopped for a time to allow their liver to recover. Once their liver has recovered treatment will need to be started again - ‘reintroduced’.
NICE TB guidelines recommend that all 4 drugs are reintroduced. The American Thoracic Society guidelines differ. These recommend that the drug pyrazinamide (Z) is left out, as it is thought to make DILI more likely. Although this three-drug treatment is still effective, it needs to be taken over nine months. This is more difficult for patients & more costly to the NHS. Currently, clinicians in the UK & globally choose between the two guidelines; some reintroduce Z whilst others do not.
This research will answer which of the 2 treatment options
a) leads to fewer patients experiencing DILI?
b) results in a better quality of life for patients?
c) offers better use of limited NHS resources?The research will be conducted over 4 years across a number of hospital clinics in the UK. The research will include 350 adults who experience DILI whilst on standard TB treatment, with 90 enrolled for each year of the study. Patients will be selected at random to be in either one of two groups for the study. One group will have 4 drugs reintroduced (i.e. including Z). The other group will have only 3 drugs reintroduced, (i.e. excluding Z). Patients and clinicians will know which treatment they are getting. The trial primary outcome will be a laboratory-based measure of the number of patients that experience the return of DILI.
Patients medical records are checked for DILI recurrence and their quality of life will be measured using the EQ5D.
REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
22/NE/0111
Date of REC Opinion
26 Jul 2022
REC opinion
Favourable Opinion